Evidence map›Paper›PMID 23588715›Full record

ArticleLeukemia2014

CRM1 inhibition induces tumor cell cytotoxicity and impairs osteoclastogenesis in multiple myeloma: molecular mechanisms and therapeutic implications.

Y-T Tai, Y Landesman, C Acharya, Y Calle, M Y Zhong, M Cea, D Tannenbaum, A Cagnetta, M Reagan, A A Munshi and 14 more

Open access · bronzeAbstract read
In one paragraph

Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 202 papers.

0numbers the graph read from it
0cells of the map it votes in
202citing papers in PubMed
11.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

202 citing papers in PubMed, 302 citations in OpenAlex.

  1. Trial
  2. Phase I/II Trial of Exportin 1 Inhibitor Selinexor plus Docetaxel in Previously Treated, Advanced KRAS-Mutant Non-Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
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  7. Preclinical Assessment with Clinical Validation of Selinexor with Gemcitabine and Nab-Paclitaxel for the Treatment of Pancreatic Ductal Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Trial
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  9. Selective Inhibition of Nuclear Export With Oral Selinexor for Treatment of Relapsed or Refractory Multiple Myeloma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018
    Trial
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142 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 5 institutions in 2 countries.

Y-T TaiLeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Y LandesmanDepartment of Biology, Karyopharm Therapeutics Inc, Natick, MA, USA.
C AcharyaLeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Y CalleDepartment of Haematological Medicine, King's College London, London, UK.
M Y ZhongLeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
M CeaLeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
D TannenbaumLeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
A CagnettaLeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
M ReaganLeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
A A MunshiLeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
W SenapedisDepartment of Biology, Karyopharm Therapeutics Inc, Natick, MA, USA.
J R Saint-MartinDepartment of Biology, Karyopharm Therapeutics Inc, Natick, MA, USA.
T KashyapDepartment of Biology, Karyopharm Therapeutics Inc, Natick, MA, USA.
S ShachamDepartment of Biology, Karyopharm Therapeutics Inc, Natick, MA, USA.
M KauffmanDepartment of Biology, Karyopharm Therapeutics Inc, Natick, MA, USA.
Y GuDepartment of Molecular Genetics and Microbiology, Shands Cancer Center, University of Florida, Gainesville, FL, USA.
L WuDepartment of Molecular Genetics and Microbiology, Shands Cancer Center, University of Florida, Gainesville, FL, USA.
I GhobrialLeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
F ZhanDivision of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
A L KungDivision of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
S A ScheyLurie Family Imaging Center, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
P RichardsonLeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
N C MunshiLeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
K C AndersonLeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Dana-Farber Cancer Institute · USKaryopharm Therapeutics (United States) · USUniversity of Florida Health · USUniversity of Iowa · USKing's College London · GB

Funding

Trageting the Multiple Myeloma EpigenomeP50CA100707 · NCI · DANA-FARBER CANCER INSTITUTE · PI ANDERSON, KENNETH C., MUNSHI, NIKHIL C. · 2003 to 2023
$45.0M
Targeting Genomic Instability and Evolution in MyelomaP01CA155258 · NCI · DANA-FARBER CANCER INST · PI Jill Corre · 2011 to 2026
$32.5M
Targeting Myeloma Cell-Host Bone Marrow InteractionsP01CA078378 · NCI · DANA-FARBER CANCER INSTITUTE · PI RITZ, JEROME · 1998 to 2014
$26.2M
NCI NIH HHS P01 CA078378NCI NIH HHS P01 CA155258NCI NIH HHS P50 CA100707NCI NIH HHS P50CA100707PHS HHS P01-78378PHS HHS R0-1 50947
6 · The paper itself

Abstract

The key nuclear export protein CRM1/XPO1 may represent a promising novel therapeutic target in human multiple myeloma (MM). Here we showed that chromosome region maintenance 1 (CRM1) is highly expressed in patients with MM, plasma cell leukemia cells and increased in patient cells resistant to bortezomib treatment. CRM1 expression also correlates with increased lytic bone and shorter survival. Importantly, CRM1 knockdown inhibits MM cell viability. Novel, oral, irreversible selective inhibitors of nuclear export (SINEs) targeting CRM1 (KPT-185, KPT-330) induce cytotoxicity against MM cells (ED50<200 nM), alone and cocultured with bone marrow stromal cells (BMSCs) or osteoclasts (OC). SINEs trigger nuclear accumulation of multiple CRM1 cargo tumor suppressor proteins followed by growth arrest and apoptosis in MM cells. They further block c-myc, Mcl-1, and nuclear factor κB (NF-κB) activity. SINEs induce proteasome-dependent CRM1 protein degradation; concurrently, they upregulate CRM1, p53-targeted, apoptosis-related, anti-inflammatory and stress-related gene transcripts in MM cells. In SCID mice with diffuse human MM bone lesions, SINEs show strong anti-MM activity, inhibit MM-induced bone lysis and prolong survival. Moreover, SINEs directly impair osteoclastogenesis and bone resorption via blockade of RANKL-induced NF-κB and NFATc1, with minimal impact on osteoblasts and BMSCs. These results support clinical development of SINE CRM1 antagonists to improve patient outcome in MM.

Indexed as

Exportin 1 ProteinHumansKaryopherinsMultiple MyelomaOsteoclastsReceptors, Cytoplasmic and NuclearExportin 1 ProteinKaryopherinsReceptors, Cytoplasmic and Nuclear

Identifiers

PMID23588715
PMCPMC3883926
OpenAlexW2094088075

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.